Protective effect of myostatin gene deletion on aging-related muscle metabolic decline.

While myostatin gene deletion is a promising therapy to fight muscle loss during aging, this approach induces also skeletal muscle metabolic changes such as mitochondrial deficits, redox alteration and increased fatigability. In the present study, we evaluated the effects of aging on these features in aged wild-type (WT) and mstn knockout (KO) mice. Moreover, to determine whether an enriched-antioxidant diet may be useful to prevent age-related disorders, we orally administered to the two genotypes a melon concentrate rich in superoxide dismutase for 12 weeks. We reported that mitochondrial functional abnormalities persisted (decreased state 3 and 4 of respiration; p<0.05) in skeletal muscle from aged KO mice; however, differences with WT mice were attenuated at old age in line with reduced difference on running endurance between the two genotypes. Interestingly, we showed an increase in glutathione levels, associated with lower lipid peroxidation levels in KO muscle. Enriched antioxidant diet reduced the aging-related negative effects on maximal aerobic velocity and running limit time (p<0.05) in both groups, with systemic adaptations on body weight. The redox status and the hypertrophic phenotype appeared to be beneficial to KO mice, mitigating the effect of aging on the skeletal muscle metabolic remodeling.

Oxidative stress in rats fed a high-fat high-sucrose diet and preventive effect of polyphenols: Involvement of mitochondrial and NAD(P)H oxidase systems.

Mitochondrial and NADPH oxidase systems and oxidative stress were investigated in 12 week high-fat high-sucrose (HFHS) diet-fed rats. A protective effect of wine polyphenol (PP) extract was also examined. In liver, maximal activities of CII and CII+III mitochondrial complexes were decreased but NADPH oxidase expression (p22(phox) and p47(phox)) and NADPH oxidase-dependent superoxide anion production were not modified, whereas oxidative stress (lipid and protein oxidation products and antioxidant systems) was increased with HFHS diet. In muscle, anion superoxide production was slightly increased while mitochondrial complex activities and lipid and protein oxidation products were not modified with HFHS diet. In heart, NADPH oxidase expression and superoxide anion production were increased, and maximal activity of mitochondrial respiratory chain complexes or oxidative stress parameters were not modified. Wine polyphenol extract had an inhibiting effect on liver oxidative stress and on heart NADPH oxidase expression and superoxide anion production, and on induction of hepatic steatosis with HFHS diet. Induction of mitochondrial dysfunction could be a primary event in the development of oxidative stress in liver, while in skeletal muscle and in heart the NADPH oxidase system seems to be mainly involved in oxidative stress. Wine polyphenol extract was shown to partially prevent oxidative stress in liver and heart tissues and to nearly completely prevent steatosis development in liver.

Magnesium and neoplasia: from carcinogenesis to tumor growth and progression or treatment.

Magnesium is involved in a wide range of biochemical reactions that are crucial to cell proliferation, differentiation, angiogenesis, and apoptosis. Changes in magnesium availability have been shown to influence biological responses of immuno-inflammatory cells. Equally plausible seems to be an involvement of magnesium in the multistep and interconnected processes that lead to tumor formation and development; however, the "how" and "when" of such an involvement remain to be defined. Here, we reviewed in vitro and in vivo data that indicated a role for magnesium in many biological and clinical aspects of cancer (from neoplastic transformation to tumor growth and progression or pharmacologic treatment). In adopting this approach we went through a full circle from molecular aspects to observational or epidemiological studies that could reconcile in a unifying picture the otherwise fragmentary or puzzling data currently available on the role of magnesium in cancer.

Effect of daily versus twice weekly long-term iron supplementation on iron absorption and status in iron-deficient women: a stable isotope study.

OBJECTIVES: This work aims at studying the effect of daily versus twice weekly long-term Fe supplementation on Fe absorption and status in Fe-deficient women. DESIGN AND METHODS: The study design is a randomized controlled open study carried out in the Internal Medicine Department, CHU de Clermont-Ferrand, France. Twenty-four young women participated in this study and were randomized into two groups: Group 1 received 50 mg Fe daily, and group 2 received 50 mg Fe twice weekly for 3 months. On day 10 (D10) and on day 90 (D90) of Fe supplementation, blood samples were obtained, and women received orally about 5 mg of 57Fe, and blood was sampled at different times over 24 h. The 57Fe absorption was evaluated by calculating the areas under the curves (AUC). Fe and oxidative stress status were also assessed. RESULTS: 57Fe absorption was similar in both groups on D10 but was greatly decreased in Group 1 and remained high in Group 2 on D90. Fe status was more improved in Group 1 than in Group 2. Oxidative stress status remained statistically unchanged. CONCLUSIONS: Our study shows that daily Fe supplementation is able to correct an Fe deficiency much more than twice weekly Fe supplementation in young women.

Impact of micronutrient dietary intake and status on intestinal zinc absorption in late middle-aged men: the ZENITH study.

BACKGROUND: Adjustments in intestinal absorption and losses of zinc (Zn) are thought to maintain Zn homeostasis when dietary intake levels are altered. Zn status may also influence efficiency of intestinal Zn absorption. OBJECTIVES: To determine the impact of dietary intake and status of some micronutrients on Zn absorption in late middle-aged men. DESIGN AND PARTICIPANTS: Dietary intake and status of Zn, Cu, Fe, vitamin A, C and fibre, and absorption of Zn were measured in 48 men, aged 58-68 y, confined to a metabolic unit and consuming a typical French diet. Dietary intake was estimated using 4-day food-intake records (including the weekend) and the GENI program. To assess Zn status, serum, erythrocyte, urine Zn levels and serum alkaline phosphatase activity were determined. Zn absorption was determined using the isotope double-labelling method. Zn stable isotopic ratios were measured in plasma samples collected before and 48 h after isotope administration using ICP/MS. RESULTS: Zn intake within the group of men varied from 5.7 to 20.5 mg/day and averaged 12.9 mg/day. Serum Zn level varied from 10 to 18 micromol/l and averaged 12.9 micromol/l. Zn absorption varied from 12 to 46% and averaged 29.7%. Zn absorption was not significantly (P > 0.05) correlated with Zn intake or with any of the Zn status parameters. Zn absorption was only slightly negatively correlated with serum and erythrocyte Zn levels and with serum Fe and ferritin levels in this study. CONCLUSION: Zn dietary intake and Zn absorption were satisfactory and led to an adequate Zn status in this population.

Erythrocyte magnesium influx and efflux in solid tumor bearing mice.

Mg metabolism is modified in tumors and tumor-bearing organisms. In particular cancer patients often display elevated erythrocyte Mg levels. For a better understanding of the increased erythrocyte Mg content, we attempted to determine Mg fluxes in erythrocytes from tumor-bearing mice by Mg stable isotopes, using a method developed in our laboratory. To characterize the animal Mg status, blood and tissue Mg levels and hematological parameters were assayed. Results showed that in tumor-bearing mice total erythrocyte Mg was about 46% higher than in controls, whereas plasma and tissues Mg levels were not modified; red blood cells and hemoglobin as well as hematocrits were significantly decreased, while mean corpuscular volume and mean corpuscular hemoglobin were slightly but significantly increased in tumor-bearing mice compared to controls (by 3% and 4%, respectively), a picture corresponding to a normochromic, slightly macrocytic anemia. Erythrocyte Mg efflux was about 20% higher (404 + 59 versus 330 + 45 micromol/L, respectively, p < 0.05) in tumor-bearing mice compared to controls, whereas influx was not significantly modified (130 + 11 versus 122 + 19 micromol/L, respectively). Our data therefore exclude that the increased Mg content observed in erythrocytes of tumor-bearing mice is due to decrease of Mg efflux, or to an increase of Mg influx. On the other hand, the increased Mg content observed in erythrocytes of tumor-bearing mice could simply result from an increase of young Mg-enriched erythrocytes produced by the enhanced erythropoiesis which follows tumor-induced anemia.

Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.

Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation. This study aimed to investigate the bioavailability of different forms of Mg in rats using Mg stable isotopes. Eighty male Wistar rats aged 6 weeks were fed a semi-purified Mg-depleted diet for three weeks. The rats were then randomised into ten groups and received, for two more weeks, the same diet repleted with Mg (550 mg Mg/kg) as: oxide, chloride, sulphate, carbonate, acetate, pidolate, citrate, gluconate, lactate or aspartate. After 10 days of Mg-repleted diet, the rats received orally 1.8 mg of an enriched 26Mg. Faeces and urine were then collected for 4 consecutive days. Isotope ratios in faeces and urine were determined. The Mg absorption values obtained varied from 50% to 67%. Organic Mg salts were slightly more available than inorganic Mg salts. Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied. Urinary 26Mg excretion varied from 0.20 mg to 0.33 mg, and feeding with the organic pidolate, citrate, gluconate and aspartate salts resulted in higher urinary 26Mg excretion than with inorganic salts. Ultimately, 26Mg retention was higher in the rats receiving the organic salts such as gluconate, lactate and aspartate than in those receiving the inorganic salts. Taken together, these results indicate that 26Mg is sufficiently bioavailable from the ten different Mg salts studied in the present experiment, although Mg gluconate exhibited the highest bioavailability under these experimental conditions.

Stimulatory effect of inulin on intestinal absorption of calcium and magnesium in rats is modulated by dietary calcium intakes short- and long-term balance studies.

Previous studies have shown that short-term intake of fermentable oligosaccharides (OS), including inulin, can increase mineral intestinal absorption in humans and animals. While the stimulatory effect of these substances on intestinal magnesium (Mg) absorption is generally high and consistent, their effect on calcium (Ca) seems to depend on experimental conditions, particularly the duration of fermentable OS intake. The aim of this study was to determine how the short- and long-term dietary Ca intake may modulate the effect of inulin on Ca absorption. Sixty male Wistar rats, weighing 275 g, were randomized into two groups to receive or not 10% of inulin in their diet. Each group was divided into three sub-groups to receive one of the following dietary Ca levels 0.25%, 0.50% and 0.75% in their food. The animals were fed fresh food and water ad libitum for 40 days. Apparent intestinal absorptions of Ca and Mg were determined at D13 and D36 of the experiment. As expected, inulin feeding increased Ca and Mg absorption in both periods at all dietary Ca levels. However, the effect of inulin on intestinal Ca absorption was dependent on dietary Ca levels and on experiment duration. In the short-term period, the inulin effect was prominent in the groups receiving high or low Ca levels, but in long-term period inulin improved intestinal Ca absorption much more in the group receiving the low Ca level. In addition, efficiency of intestinal absorption of Ca and Mg (%) was negatively affected by Ca intake levels. These results show that the beneficial effect of inulin on intestinal Ca absorption may be more marked in cases where the Ca intake is low or where the organism's Ca requirement is high. Further studies are required to confirm these results in humans.

Magnesium metabolism in mice selected for high and low erythrocyte magnesium levels.

A genetic control of blood magnesium (Mg) levels has been suggested. To investigate the mechanisms and the biologic significance of this genetic regulation, a mouse model, ie, mice selected for low magnesium level (MGL) and high magnesium level (MGH), was developed. The purpose of this study was to explore the Mg status and Mg metabolism in female MGL and MGH mice. We observed that MGL mice had reduced total and ionized plasma Mg, lower erythrocyte Mg, lower tibia, and kidney Mg levels. In contrast, total urinary Mg and (25)Mg levels were significantly higher in MGL mice. MGL mice had smaller total Mg exchangeable pool masses compared with MGH, and fractional transport rates of Mg (exchange constant) were different. In vitro (25)Mg enrichments in erythrocytes from MGL mice were significantly lower. Moreover, Mg efflux from erythrocytes was significantly higher in MGL. In conclusion, this work demonstrates that MGL mice present lower body stores of Mg than MGH mice and lower body Mg retention. This is confirmed at a cellular level by a lower enrichment of (25)Mg in erythrocytes. The lower retention of Mg by MGL erythrocyte in comparison to MGH appears to be partly due to a higher Mg efflux in MGL erythrocyte. It can be hypothesized that a genetic factor that modulates Na(+)/Mg(2+) exchanger activity may be important in the regulation of Mg metabolism. Further investigations on the mechanisms responsible for differences in Mg retention between MGL and MGH mice could contribute to a better understanding of the genetic regulation of cellular Mg.

Divergence in plasmatic and urinary isoprostane levels in type 2 diabetes.

BACKGROUND: Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate isoprostane levels in plasma and in urine in type 2 diabetic patients, and to compare them to other currently used biomarkers of oxidative stress. METHODS: The work was performed in a control group (n = 10) and in a type 2 diabetic group (n = 10). Besides the traditional biochemical parameters, we evaluated the plasma and urine levels of isoprostanes and malondialdehyde (MDA) as markers of oxidative stress. RESULTS: We found increased plasma and urine MDA in the diabetic patients and almost significantly decreased plasma vitamin E. Urinary isoprostane levels in diabetic patients were increased but they presented a strong tendency to a decrease in plasma isoprostanes. It is therefore suggested that, in the studied diabetic patients, although the production of isoprostanes in the body was increased (as other plasma oxidative stress biomarkers were altered) it did not lead to an increase in plasma isoprostane levels. It could be hypothesised that this results from an increased elimination of this metabolite and therefore an increased excretion in urine. CONCLUSION: Our results showed that the measurement of same oxidative stress biomarker, isoprostane, in two different biologic fluids, plasma and urine, led to divergent results and emphasised the importance to measure a biomarker both in the circulation fluid (plasma) and in the elimination fluid (urine), to have a general idea of what is occurring in the organism.

Five-week intake of short-chain fructo-oligosaccharides increases intestinal absorption and status of magnesium in postmenopausal women.

Fermentable carbohydrates have been shown to be nondigestible by human enzymes in the small intestine but are fermented extensively in the large bowel to short-chain fatty acids (SCFAs), which can increase mineral absorption. It has been shown that feeding such carbohydrates including short-chain fructo-oligosaccharides (sc-FOSs) increases intestinal magnesium (Mg) absorption in animals, but their beneficial impact on Mg absorption in humans still remains to be established. Therefore, this work aimed to investigate the effect of moderate daily doses of sc-FOSs (10 g/day) on the intestinal absorption and status of Mg in postmenopausal women without hormone replacement therapy (HRT). Eleven healthy postmenopausal women aged 59 +/- 6 years (mean +/- SD) received for 5 weeks sc-FOS or sucrose (placebo) treatments according to a randomized, double-blind, crossover design separated by a washout period of at least 3 weeks. Subjects ingested 87.5 mg of stable isotope 25Mg together with a fecal marker. Subsequently, feces were collected for 5-7 days. An inductively coupled plasma mass spectrometer (ICP/MS) was used for 25Mg stable isotope measurements in feces, urine, and blood. Mg levels were assessed also at the beginning and at the end of each treatment in plasma, erythrocytes, and urine. These measurements allowed for the determination of net intestinal Mg absorption and Mg status. The results show that the addition of 10 g sc-FOS to the diet increased Mg absorption by 12.3%, from 30.2 +/- 5.0% (placebo treatment) to 33.9 +/- 7.2% (sc-FOS treatment; mean +/- SD; p < 0.02). This increase in intestinal Mg absorption was accompanied by an increase in plasma 25Mg level and led to a higher urinary 25Mg excretion. This is the first time that such an effect is shown in humans. The overall conclusion of this work is that the ingestion of moderate doses of sc-FOS did improve intestinal Mg absorption and status in postmenopausal women. Because of the important role of Mg in many cellular functions, such Mg absorption improvement may be particularly interesting when the dietary intake of Mg is limited.

Mineral supplementation of white wheat flour is necessary to maintain adequate mineral status and bone characteristics in rats.

This experiment was designed to compare the effect of ingestion of a wheat flours on mineral status and bone characteristics in rats. White flour was tested either without further mineral supplementation or with Mg, Fe, Zn and Cu supplementation. The flour diets were compared to a control purified diet. Four groups of 10 male Wistar rats each were fed one of the experimental diets for 6 wk and mineral status and tissue retention as well as bone characteristics were determined. As expected, mineral intake, except for calcium, was significantly lesser in rats fed the white flour diet than in the other groups. The rats fed the white flour diet had the lowest food intake, weight gain, fecal excretion and intestinal fermentation. The most important result was that Mg and Fe status were drastically lower in rats fed the white flour diet than in those fed whole flour or control diets. The status of these both elements were significantly improved by the mineral supplementation of white flour. There were no major significant differences between mineral-supplemented white flour and whole flour groups in mineral status. Furthermore, bone mineral densities (total, metaphyseal and diphyseal) were significantly lower in rats fed white flour diet compared to the other diet groups, while no significant difference was observed between the mineral-supplemented white flour, whole flour or control diet groups. In conclusion, the present work shows clearly the importance of mineral-supplementation of white wheat flour to sustain an adequate intake of minerals. Our results indicate also that the whole wheat flour did not negatively alter mineral bioavailability, in comparison to mineral supplemented white flour. Clinical studies are still needed to confirm these rat results in human.

Fructooligosaccharides enhance mineral apparent absorption and counteract the deleterious effects of phytic acid on mineral homeostasis in rats.

Phytic acid (PA) and fructooligosaccharides (FOS) such as inulin are two food components that are able to modify mineral absorption negatively or positively. The influence of PA and FOS on the cecal and apparent mineral absorption as well as on the mineral status (plasma, hepatic, and bone) were investigated in four groups of rats fed one of the experimental diets: a fiber-free (FF) diet, a FF diet containing 7 g/kg PA (FF + PA), a diet containing 100 g/kg inulin (FOS), or a FOS diet containing 7 g/kg PA (FOS + PA). The cecal enlargement together with the acidification of cecal pH in rats adapted to FOS diets led to an improved Ca and Mg cecal absorption. Mineral apparent absorption was significantly enhanced by FOS ingestion (Ca, +20%; Mg, +50%; Fe, +23%; Cu, +45%), whereas PA decreased this factor only for trace elements (Fe, -48%; Zn, -62%; Cu, -31%). These inhibitory effects of a FF + PA diet have repercussions on blood (Mg, -15%; Fe, -12%; transferrin saturation -31%), liver (Mg, -18%; Fe, -42%; Zn, -25%), and bone (Zn, -25%) variables. However, the introduction of FOS into a PA diet counteracted these observed deleterious effects by stimulating bacterial hydrolysis of PA (+60% in rats adapted to FOS + PA compared to those fed the FF + PA diet) and by improving cecal absorption of minerals.

Compartmental analysis of magnesium kinetics in Mg-sufficient and Mg-deficient rats.

In this study, we determined magnesium kinetic values in normal rats using stable-isotope techniques. Additionally, we calculated the mass of the exchangeable pools of Mg in Mg-deficient rats to determine whether it can be used as a marker of Mg status. Rats were fed either a control diet (1,000 mg Mg/kg) or a Mg-deficient diet (60 mg Mg/kg). After 2 weeks on the experimental diets, each rat received an intravenous injection of 26Mg. The plasma Mg disappearance curve over the next 7 days was used to measure the mass and fractional transport rate of 3 rapidly exchanging Mg metabolic pools. In control rats, the mass of pool 1 (1.37 mg) was half that of pool 2 (2.46 mg), and pool 3 (47.7 mg) accounted for greater than 90% of exchangeable Mg. In Mg-deficient rats, we observed a significant decrease in the size of the 3 exchangeable pools of Mg (0.36, 0.72, and 20.2 mg, respectively) relative to the control rats. Furthermore, the fractional transport rate of Mg from pool 1 to pool 3 in Mg-deficient rats was 3 times the rate in the control rats, and the rate of irreversible loss from pool 1 was lower in Mg-deficient rats. In summary, this study allows us to establish Mg kinetic data in Mg-sufficient and Mg-deficient rats. The present experiment supports the conclusion that the isotopic test identifies animals with severe Mg deficiency.

Exchangeable magnesium pool masses reflect the magnesium status of rats.

A sensitive and valid marker to assess magnesium (Mg) status in humans is not available. The kinetically determined exchangeable pool masses have been used for other minerals, such as zinc and selenium, as markers of whole-body mineral status. To evaluate the validity of this relationship for Mg, we measured the exchangeable pools of Mg in rats over a range of magnesium dietary intakes. Rats weighing approximately 170 g were fed a control diet (500 mg Mg/kg), a marginally Mg-deficient diet (200 mg/kg) or a severely Mg-deficient diet (60 mg Mg/kg) for 2 wk. Subsequently, rats were administered an intravenous injection of (25)Mg, and the plasma (25)Mg disappearance curve was followed for the next 7 d. The following two methods were employed to analyze the exchangeable pools of Mg: 1) formal compartmental modeling and 2) a simplified determination of the total mass of the rapidly exchangeable Mg pool (EMgP). The mass of the three exchangeable pools (two extracellular pools and one intracellular pool) determined by compartmental analysis decreased in proportion to dietary Mg intake. EMgP, the combined pools of Mg that exchange with the plasma Mg within 48 h, decreased significantly as dietary Mg was lowered. It was positively correlated with conventional markers of Mg status (total Mg in plasma, erythrocyte and tibia Mg levels). Compartmental analysis assesses Mg exchangeable pools more accurately, but determination of EMgP is simpler and faster. Our findings demonstrate that the exchangeable pools of Mg constitute a good marker of Mg status in rats.

Response of diamine oxidase and other plasma copper biomarkers to various dietary copper intakes in the rat and evaluation of copper absorption with a stable isotope.

There is a lack of agreement on index of Cu status and reliable and sensitive biomarkers are still required. The purpose of this present work was to assess in rats the sensitivity of diamine oxidase (DAO) activity, a recently proposed biomarker, to modifications in dietary Cu intake in comparison with other plasma biomarkers of Cu status. We also evaluated the effect of Cu dietary level on Cu and Zn intestinal absorption. Results showed that plasma Cu and plasma caeruloplasmin were significantly decreased at day 8 compared with the control group (7.4 mg Cu/kg diet) while DAO activity was significantly decreased at day 12 of the deficient diet (0.61 mg Cu/kg diet). Cu supplementation (35 mg Cu/kg diet) had no effect on any of the studied biomarkers of Cu status. In Cu-deficient rats plasma Cu and DAO activities were normalized 4 d after return to the control diet while caeruloplasmin was normalized later, at day 11. Apparent absorption values (%) of total Cu or 65Cu isotope were significantly increased in the Cu-deficient rats compared with the other groups and similar in the control and the Cu-supplemented groups. The urinary excretion of total Cu or 65Cu isotope were increased in the Cu-supplemented group compared with the other two groups. Both apparent absorption and urinary excretion of total Zn or 67Zn isotope remained unchanged in the three experimental groups. In conclusion, DAO activity seemed to be less sensitive to Cu deficiency than plasma Cu or caeruloplasmin concentrations. The present study also showed a significant increase in Cu intestinal absorption with dietary Cu restriction but no decrease with Cu supplementation in the rat.

Long-term consumption of red wine does not modify intestinal absorption or status of zinc and copper in rats.

Red wines contain many components such as polyphenols and ethanol that may influence mineral absorption. We report on studies in a rat model that were designed to investigate the extent to which short- and long-term intake of red wine or ethanol may influence (67)Zn and (65)Cu absorption in rats. Rats (n = 96) were divided into three groups, a control group that received demineralized water, a group that received red wine diluted with water (v/v) and an ethanol group that received 6% ethanol. Half of each group was used for the short-term study; the others were used for the long-term study. After 3 d (short-term study) or 28 d (long-term study) of beverage consumption, the rats were gavaged with 2 mL of solution containing 2027 nmol (67)Zn and 902 nmol (65)Cu. Subsequently, 3-d urinary and fecal collections were performed and analyzed for total and isotopic Zn and Cu. In the long-term study, blood, tibia and liver were also sampled for mineral status assessment. Neither short- nor long-term intake of red wine altered (67)Zn or (65)Cu absorption. In contrast, long-term (but not short-term) ethanol consumption significantly increased both (67)Zn and (65)Cu absorption compared with the control and red wine groups. The long-term consumption of ethanol or red wine did not affect blood or tissue Zn or Cu levels. In conclusion, short- or long-term consumption of red wine did not have a negative effect on intestinal absorption or tissue levels of zinc and Cu in rats.

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

Plasma levels of 8-epiPGF2alpha, an in vivo marker of oxidative stress, are not affected by aging or Alzheimer's disease.

Free radicals are likely involved in the aging process and there is a growing body of evidence that free radical damage to cellular function is associated with a number of age-related diseases such as atherosclerosis, cancer, and neurologic disorders. The present study was designed to evaluate in a healthy population the evolution with age of 8-epiPGF2alpha plasma levels, a recently proposed marker of in vivo lipid peroxidation. Moreover we investigated this marker of oxidative stress in patients with Alzheimer's disease (AD), an age-related neurodegenerative disorder in the development of which free radicals have been involved. Our results show that in the healthy population studied, despite decreased antioxidant defenses with increasing age as monitored by antioxidant capacity measurement, plasma 8-epiPGF2alpha levels were not correlated with age. Moreover, we have demonstrated that AD patients presented no modification of plasma 8-epiPGF2alpha level and no major alteration of the antioxidant status. In conclusion, the measurement of plasma 8-epiPGF2alpha did not allow us to detect alterations in oxidative stress with aging or in AD.

Lipid peroxidation and antioxidant status in experimental diabetes.

Oxidative stress is currently suggested as a mechanism underlying diabetes. The present study was designed to evaluate the oxidative stress related parameters in streptozotocin-induced diabetes in rats using different complementary approaches: susceptibility to in vitro oxidation (lipid peroxidation induction in liver homogenate, red blood cells hemolysis), blood antioxidant status (total antioxidant capacity by two approaches), and plasma isoprostane measurement, a new marker of lipid peroxidation in vivo. We have shown that induced liver thiobarbituric acid reactive substances increased after 4 weeks of diabetes, in spite of increased liver vitamin E content. Red blood cells hemolysis was significantly delayed after 4 weeks of diabetes. Plasma antioxidant capacity (AOC) tended to increase after 4 weeks of diabetes and was correlated with plasma vitamin E levels. Total antioxidant activity (TAA) significantly decreased after 1 week and a significant correlation was observed with plasma albumin levels. Plasma isoprostane (8-epiprostaglandinF2alpha) concentrations were not modified significantly 1 week or 4 weeks after the induction of diabetes. Levels of vitamin E in the diet and changes in its distribution among the body seems to play an important role in the development of oxidative stress during diabetes and its consequences.